The Good Laboratory Practice Regulations, 2003

Suppliment tal-Gazzetta tal-Gvern ta’ Malta, Nru. 17,468, 5 ta’ Settembru, 2003

L.N. 234 of 2003

PRODUCT SAFETY ACT

(ACT NO. V OF 2001)

The Good Laboratory Practice Regulations, 2003

IN exercise of the powers conferred by article 39 of the Product

Safety Act, the Minister for Finance and Economic Affairs has, on the

advice of the Malta Standards Authority, made the following regulations>

The title of these Regulations is the Good Laboratory Citation.

Practice Regulations, 2003.

Laboratories carrying out tests on chemical products, in General Provisions

THE OECD PRINCIPLES OF GOOD LABORATORY PRACTICE (GLP)

Contents

Section I

INTRODUCTION

Preface

1. Scope

2. Definitions of terms

2.1. Good laboratory practice

2.2. Terms concerning the organisation of a test facility

2.3. Terms concerning the non-clinical health and environmental safety study

2.4. Terms concerning the test item

Section II

GOOD LABORATORY PRACTICE PRINCIPLES

1. Test facility organisation and personnel

1.1. Test facility management’s responsibilities

1.2. Study director’s responsibilities

1.3. Principal investigator’s responsibilities

1.4. Study personnel’s responsibilities

2. Quality assurance programme

2.1. General

2.2. Responsibilities of the quality assurance personnel

3. Facilities

3.1. General

3.2. Test system facilities

3.3. Facilities for handling test and reference items

3.4. Archive facilities

3.5. Waste disposal

4. Apparatus, material, and reagents

5. Test systems

5.1. Physical/chemical

5.2. Biological

6. Test and reference items

6.1. Receipt, handling, sampling and storage

6.2. Characterisation

7. Standard operating procedures

8. Performance of the study

8.1. Study plan

8.2. Content of the study plan

8.3. Conduct of the study

9. Reporting of study results

9.1. General

9.2. Content of the final report

10. Storage and retention of records and materials

Section I

INTRODUCTION

Preface

Government and industry are concerned about the quality of non-clinical health and

environmental safety studies upon which hazard assessments are based. As a

consequence, OECD Member countries have established criteria for the performance

of these studies.

To avoid different schemes of implementation that could impede international trade in

chemicals, OECD Member countries have pursued international harmonisation of test

methods and good laboratory practice. In 1979 and 1980 an international group of

experts, established under the special programme on the control of chemicals, developed

the ‘OECD principles of good laboratory practice’ (GLP), utilising common managerial

and scientific practices and experience from various national and international sources.

These principles of GLP were adopted by the OECD Council in 1981, as an Annex to

the Council Decision on the mutual acceptance of data in the assessment of chemicals.

[C(81)30(Final)].

In 1995 and 1996, a new group of experts was formed to revise and update the principles.

The current document is the result of the consensus reached by that group. It cancels

and replaces the original principles adopted in 1981.

The purpose of these principles of good laboratory practice is to promote the

development of quality test data. Comparable quality of test data forms the basis for

the mutual acceptance of data among countries. If individual countries can confidently

rely on test data developed in other countries, duplicative testing can be avoided, thereby

saving time and resources. The application of these principles should help to avoid the

creation of technical barriers to trade, and further improve the protection of human

health and the environment.

1. Scope

These principles of good laboratory practice should be applied to the non-clinical safety

testing of test items contained in pharmaceutical products, pesticide products, cosmetic

products, veterinary drugs as well as food additives, feed additives, and industrial

chemicals. These test items are frequently synthetic chemicals, but may be of natural

or biological origin and, in some circumstances, may be living organisms. The purpose

of testing these test items is to obtain data on their properties and/or their safety with

respect to human health and/or the environment.

Non-clinical health and environmental safety studies covered by the principles of good

laboratory practice include work conducted in the laboratory, in greenhouses, and in

the field.

Unless specifically exempted by national legislation, these principles of good laboratory

practice apply to all non-clinical health and environmental safety studies required by

regulation for the purpose of registering or licensing pharmaceuticals, pesticides, food

and feed additives, cosmetic products, veterinary drug products and similar products,

and for the regulation of industrial chemicals.

2. Definition of terms

2.1. Good laboratory practice

Good laboratory practice (GPL) is a quality system concerned with the organisational

process and the conditions under which non-clinical health and environmental safety

studies are planned, performed, monitored, recorded, archived and reported.

2.2. Terms concerning the organisation of a test facility

1. Test facility means the persons, premises and operational unit(s) that are

necessary for conducting the non-clinical health and environmental

safety study. For multisite studies, those which are conducted at more

than one site, the test facility comprises the site at which the study

director is located and all individual test sites, which individually or

collectively can be considered to be test facilities.

2. Test site means the location(s) at which a phase(s) of a study is conducted.

3. Test facility management means the person(s) who has the authority and

formal responsibility for the organisation and functioning of the test

facility according to these principles of good laboratory practice.

4. Test site management (if appointed) means the person(s) responsible for

ensuring that the phase(s) of the study, for which he is responsible, are

conducted according to these principles of good laboratory practice.

5. Sponsor means an entity which commissions, supports and/or submits a

non-clinical health and environmental safety study.

6. Study director means the individual responsible for the overall conduct of

the non-clinical health and environmental safety study.

7. Principal investigator means an individual who, for a multisite study, acts

on behalf of the study director and has defined responsibility for

delegated phases of the study. The study director’s responsibility for

the overall conduct of the study cannot be delegated to the principal

investigator(s); this includes approval of the study plan and its

amendments, approval of the final report, and ensuring that all applicable

principles of good laboratory practice are followed.

8. Quality assurance programme: means a defined system, including

personnel, which is independent of study conduct and is designed to

assure test facility management of compliance with these principles of

good laboratory practice.

9. Standard operating procedures (SOPs) means documented procedures

which describe how to perform tests or activities normally not specified

in detail in study plans or test guidelines.

10. Master schedule means a compilation of information to assist in the

assessment of workload and for the tracking of studies at a test facility.

2.3. Terms concerning the non-clinical health and environmental safety study

1. Non-clinical health and environmental safety study, henceforth referred to

simply as ‘study’, means an experiment or set of experiments in which

a test item is examined under laboratory conditions or in the environment

to obtain data on its properties and/or its safety, intended for submission

to appropriate regulatory authorities.

2. Short-term study means a study of short duration with widely used, routine

techniques.

3. Study plan means a document which defines the objectives and experimental

design for the conduct of the study, and includes any amendments.

4. Study plan amendment means an intended change to the study plan after

the study initiation date.

5. Study plan deviation means an unintended departure from the study plan

after the study initiation date.

6. Test system means any biological, chemical or physical system or a

combination thereof used in a study.

7. Raw data means all original test facility records and documentation, or

verified copies thereof, which are the result of the original observations

and activities in a study. Raw data also may include, for example,

photographs, microfilm or microfiche copies, computer readable media,

dictated observations, recorded data from automated instruments, or

any other data storage medium that has been recognised as capable of

providing secure storage of information for a time period as stated in

section 10 below.

8. Specimen means any material derived from a test system for examination,

analysis, or retention.

9. Experimental starting date means the date on which the first study specific

data are collected.

10. Experimental completion date means the last date on which data are

collected from the study.

accordance with the Dangerous Substances (Notification) Regulations,

2001, shall comply with the principles of good laboratory practice as

laid down in the First Schedule to these regulations.

Regulation 2 shall apply also where other provisions provide

for the application of the principles of good laboratory practice in respect

of tests on chemical products to evaluate their safety for man and, or

the environment.

The National Accreditation Body-Malta Standards Duties

Competent

Authority (NAB-MSA), hereinafter referred to as the competent Authority

authority, shall be responsible for verifying compliance with the

principles of good laboratory practice of any testing laboratory in Malta

claiming to use GLP, as referred to in regulation 2, in the conduct of

tests on chemicals.

Should it be established on the basis of detailed evidence

that the application of the principles of good laboratory practice and the

verification of their application for tests on chemical substances show

that, although a chemical substance has been examined in accordance

with the requirements of these regulations, it presents a danger to man

and, or the environment, the Director responsible for Consumer Affairs

may, on the advice of the Head of the Directorate responsible for

Chemicals within the Malta Standards Authority, provisionally prohibit

or make subject to special conditions the marketing of that substance in

Malta.

Where a laboratory has carried out a test in accordance with

regulation 2 of these regulations, it shall give a notice in writing to the

person who commissioned the test and to the competent authority, stating

that the test has been carried out in conformity with the principles of

good laboratory practice.

1 This regulation shall apply to the inspection and verification

of the organizational processes and the conditions under which

laboratory studies are planned, performed, recorded and reported for

the non-clinical testing, carried out in accordance with the rules and

regulations, of all chemicals (e.g. cosmetics, industrial chemicals,

medicinal products, food additives, animal feed additives, pesticides)

in order to assess the effect of such products on man, animals and the

environment.

2.2 This regulation is not concerned with the interpretation and

evaluation of test results.

7.3 The compliance with GLP of any testing laboratory claiming

to use GLP in the conduct of tests on chemicals shall be verified using

the procedure laid down in this regulation.

4.4 Where the provisions of regulation 7.3 have been complied

with, and the results of the inspection and verification are satisfactory,

the competent authority may provide endorsement of a claim by a

laboratory that it and the tests that it carries out comply with GLP,

using the formula ‘Assessment of conformity with GLP according to

Directive 88#320#EEC on ‘……… (date)’.

4.5 The competent authority shall inspect the laboratory and audit

the studies in accordance with the provisions laid down in the Second

Schedule to these regulations.

4.6 The competent authority shall ensure that commercially

sensitive and other confidential information to which it gains access as

a result of GLP compliance monitoring activities is made available only

to those national and international bodies which the Minister may, from

time to time, designate, and to a laboratory or study sponsor directly

concerned with a particular inspection or study audit.

7.7 The names of the laboratories subject to inspection by the

competent authority, their GLP compliance status and the dates upon

which laboratory inspections or study audits have been conducted shall

not be considered to be confidential.

Without prejudice to regulation 9, the competent authority shall Recognition

compliance status in

accept the results of laboratory inspections and study audits on GLP other States

compliance carried out by Member States of the European Community.

Where the competent authority has sufficient reason to believe

that a laboratory in another State claiming GLP compliance has not

carried out a test according to GLP, it may request further information

from the competent authority of that State prior to taking a decision on

whether to accept the test results.

As from such date as the Minister may, by notice in the

Government Gazette, determine, the provisions of Article 6 of Council

Directive 88#320#πEEC of the European Community shall apply in

respect of measures taken pursuant to regulation 9.

Study initiation date means the date the study director signs the study plan.

Study completion date means the date the study director signs the final

report.

2.4. Terms concerning the test item

1. Test item means an article that is the subject of a study.

2. Reference item (‘control item’) means any article used to provide a basis

for comparison with the test item.

3. Batch means a specific quantity or lot of a test item or reference item

produced during a defined cycle of manufacture in such a way that it

could be expected to be of a uniform character and should be designated

as such.

4. Vehicle means any agent which serves as a carrier used to mix, disperse, or

solubilise the test item or reference item to facilitate the administration/

application to the test system.

Section II

GOOD LABORATORY PRACTICE PRINCIPLES

1. Test facility organisation and personnel

1.1. Test facility management’s responsibilities

1. Each test facility management should ensure that these principles of good

laboratory practice are complied with, in its test facility.

2. At a minimum it should

(a)

ensure that a statement exists which identifies the individual(s)

within a test facility who fulfil the responsibilities of management

as defined by these principles of good laboratory practice;

(b)

ensure that a sufficient number of qualified personnel,

appropriate facilities, equipment, and materials are available for

the timely and proper conduct of the study;

(c)

ensure the maintenance of a record of the qualifications,

training, experience and job description for each professional

and technical individual;

(d)

ensure that personnel clearly understand the functions they are

to perform and, where necessary, provide training for these

functions;

(e)

ensure that appropriate and technically valid standard operating

procedures are established and followed, and approve all original

and revised standard operating procedures;

(f)

ensure that there is a quality assurance programme with

designated personnel and assure that the quality assurance

responsibility is being performed in accordance with these

principles of good laboratory practice;

(g)

ensure that for each study an individual with the appropriate

qualifications, training, and experience is designated by the

management as the study director before the study is initiated.

Replacement of a study director should be done according to

established procedures, and should be documented;

(h)

ensure, in the event of a multisite study, that, if needed, a

principal investigator is designated, who is appropriately trained,

qualified and experienced to supervise the delegated phase(s)

of the study. Replacement of a principal investigator should be

done according to established procedures, and should be

documented;

(i)

ensure documented approval of the study plan by the study

(j)

ensure that the study director has made the approval study plan

available to the quality assurance personnel;

(k)

ensure the maintenance of a historical file of all standard

operating procedures;

(l)

ensure that an individual is identified as responsible for the

management of the archive(s);

(m)

ensure the maintenance of a master schedule;

(n)

ensure that test facility supplies meet requirements appropriate

to their use in a study;

(o)

ensure for a multisite study that clear lines of communication

exist between the study director, principal investigator(s), the

quality assurance programme(s) and study personnel;

(p)

ensure that test and reference items are appropriately

(q)

establish procedures to ensure that computerised systems are

suitable for their intended purpose, and are validated, operated

and maintained in accordance with these principles of good

laboratory practice.

3. When a phase(s) of a study is conducted at a test site, test site management

(if appointed) will have the responsibilities as defined above with the

following exceptions: 1.1.2(g), (i), (j) and (o).

1.2. Study director’s responsibilites

1. The study director is the single point of study control and has the

responsibility for the overall conduct of the study and for its final report.

2. These responsibilities should include, but not be limited to, the following

functions. The study director should

(a)

approve the study plan and any amendments to the study plan

by dated signature;

(b)

ensure that the quality assurance personnel have a copy of the

study plan and any amendments in a timely manner and

communicate effectively with the quality assurance personnel

as required during the conduct of the study;

(c)

ensure that study plans and amendments and standard operating

procedures are available to study personnel;

(d)

ensure that the study plan and the final report for a multisite

study identify and define the role of any principal investigator(s)

and any test facilities and test sites involved in the conduct of

the study;

(e)

ensure that the procedures specified in the study plan are

followed, and assess and document the impact of any deviations

from the study plan on the quality and integrity of the study, and

take appropriate corrective action if necessary; acknowledge

deviations from standard operating procedures during the

conduct of the study;

(f)

ensure that all raw data generated are fully documented and

recorded;

(g)

ensure that computerised systems used in the study have been

validated;

(h)

sign and date the final report to indicate acceptance of

responsibility for the validity of the data and to indicate the extent

to which the study complies with these principles of good

laboratory practice;

(i)

ensure that after completion (including termination) of the

study, the study plan, the final report, raw data and supporting

material are archived.

Principal investigator’s responsibilities

The principal investigator will ensure that the delegated phases of the study are

conducted in accordance with the applicable principles of good laboratory

practice.

1.4. Study personnel’s responsibilities

1. All personnel involved in the conduct of the study must be knowledgeable

in those parts of the principles of good laboratory practice which are

applicable to their involvement in the study.

2. Study personnel will have access to the study plan and appropriate standard

operating procedures applicable to their involvement in the study. It is

their responsibility to comply with the instructions given in these

documents. Any deviation from these instructions should be documented

and communicated directly to the study director, and/or if appropriate,

the principal investigator(s).

3. All study personnel are responsible for recording raw data promptly and

accurately and in compliance with these principles of good laboratory

practice, and are responsible for the quality of their data.

4. Study personnel should exercise health precautions to minimise risk to

themselves and to ensure the integrity of the study. They should

communicate to the appropriate person any relevant known health or

medical condition in order that they can be excluded from operations

that may affect the study.

2. Quality assurance programme

2.1. General

1. The test facility should have a documented quality assurance programme

to assure that studies performed are in compliance with these principles

of good laboratory practice.

2. The quality assurance programme should be carried out by an individual

or by individuals designated by and directly responsible to management

and who are familiar with the test procedures.

3. This individual(s) should not be involved in the conduct of the study being

assured.

2.2. Responsibilities of the quality assurance personnel

The responsibilities of the quality assurance personnel include, but are not

limited to, the following functions. They should

(a) maintain copies of all approved study plans and standard operating

procedures in use in the test facility and have access to an up-to-date

copy of the master schedule;

(b) verify that the study plan contains the information required for compliance

with these principles of good laboratory practice. This verification should

be documented;

(c) conduct inspections to determine if all studies are conducted in accordance

with these principles of good laboratory practice. Inspections should

also determine that study plans and standard operating procedures have

been made available to study personnel and are being followed.

Inspections can be of three types as specified by quality assurance

programme standard operating procedures

– study-based inspections,

– facility-based inspections,

– process-based inspections.

Records of such inspections should be retained;

(d)

inspect the final reports to confirm that the methods, procedures, and

observations are accurately and completely described, and that the

reported results accurately and completely reflect the raw data of the

studies;

(e) promptly report any inspection results in writing to management and to

the study director, and to the principal investigator(s) and the respective

management, when applicable;

(f) prepare and sign a statement, to be included with the final report, which

specifies types of inspections and their dates, including the phase(s) of

the study inspected, and the dates inspection results were reported to

management and the study director and principal investigator(s), if

applicable. This statement would also serve to confirm that the final

report reflects the raw data.

3. Facilities

3.1. General

1. The test facility should be of suitable size, construction and location to

meet the requirements of the study and to minimise disturbance that

would interfere with the validity of the study.

2. The design of the test facility should provide an adequate degree of

separation of the different activities to assure the proper conduct of

each study.

3.2. Test system facilities

1. The test facility should have a sufficient number of rooms or areas to assure

the isolation of test systems and the isolation of individual projects,

involving substances or organisms known to be or suspected of being

biohazardous.

2. Suitable rooms or areas should be available for the diagnosis, treatment

and control of diseases, in order to ensure that there is no unacceptable

degree of deterioration of test systems.

3. There should be storage rooms or areas as needed for supplies and

equipment. Storage rooms or areas should be separated from rooms or

areas housing the test systems and should provide adequate protection

against infestation, contamination, and/or deterioration.

3.3. Facilities for handling test and reference items

1. To prevent contamination or mix-ups, there should be separate rooms or

areas for receipt and storage of the test and reference items, and mixing

of the test items with a vehicle.

2. Storage rooms or areas for the test items should be separate from rooms or

areas containing the test systems. They should be adequate to preserve

identity, concentration, purity, and stability, and ensure safe storage for

hazardous substances.

3.4. Archive facilities

Archive facilities should be provided for the secure storage and retrieval of

study plans, raw data, final reports, samples of test items and specimens. Archive

design and archive conditions should protect contents from untimely

deterioration.

3.5. Waste disposal

Handling and disposal of wastes should be carried out in such a way as not to

jeopardise the integrity of studies. This includes provision for appropriate

collection, storage and disposal facilities, and decontamination and

transportation procedures.

4. Apparatus, material, and reagents

1. Apparatus, including validated computerised systems, used for the generation,

storage and retrieval of data, and for controlling environmental factors relevant

to the study should be suitably located and of appropriate design and adequate

capacity.

2. Apparatus used in a study should be periodically inspected, cleaned, maintained,

and calibrated according to standard operating procedures. Records of these

activities should be maintained. Calibration should, where appropriate, be

traceable to national or international standards of measurement.

3. Apparatus and materials used in a study should not interfere adversely with the

test systems.

4. Chemicals, reagents, and solutions should be labelled to indicate identity (with

concentration if appropriate), expiry date and specific storage instructions.

Information concerning source, preparation date and stability should be

available. The expiry date may be extended on the basis of documented

evaluation or analysis.

5. Test systems

5.1. Physical/chemical

1. Apparatus used for the generation of physical/chemical data should be

suitably located and of appropriate design and adequate capacity.

2. The integrity of the physical/chemical test systems should be ensured.

5.2. Biological

1. Proper conditions should be established and maintained for the storage,

housing, handling and care of biological test systems, in order to ensure

the quality of the data.

2. Newly received animal and plant test systems should be isolated until their

health status has been evaluated. If any unusual mortality or morbidity

occurs, this lot should not be used in studies and, when appropriate,

should be humanely destroyed. At the experimental starting date of a

study, test systems should be free of any disease or condition that might

interfere with the purpose or conduct of the study. Test systems that

become diseased or injured during the course of a study should be

isolated and treated, if necessary to maintain the integrity of the study.

Any diagnosis and treatment of any disease before or during a study

should be recorded.

3. Records of source, date of arrival, and arrival condition of test systems

should be maintained.

4. Biological test systems should be acclimatised to the test environment for

an adequate period before the first administration/application of the test

or reference item.

5. All information needed to properly identify the test systems should appear

on their housing or containers. Individual test systems that are to be

removed from their housing or containers during the conduct of the

study should bear appropriate identification, wherever possible.

6. During use, housing or containers for test systems should be cleaned and

sanitised at appropriate intervals. Any material that comes into contact

with the test system should be free of contaminants at levels that would

interfere with the study. Bedding for animals should be changed as

required by sound husbandry practice. Use of pest control agents should

be documented.

7. Test systems used in field studies should be located so as to avoid

interference in the study from spray drift and from past usage of

pesticides.

6. Test and reference items

6.1. Receipt, handling, sampling and storage

1. Records including test item and reference item characterisation, date of

receipt, expiry date, quantities received and used in studies should be

maintained.

2. Handling, sampling, and storage procedures should be identified in order

that the homogeneity and stability are assured to the degree possible

and contamination or mix-up are precluded.

3. Storage container(s) should carry identification information, expiry date,

and specific storage instructions.

6.2. Characterisation

1. Each test and reference item should be appropriately identified (e.g. code,

chemical abstracts service registry number (CAS number), name,

biological parameters).

2. For each study, the identity, including batch number, purity, composition,

concentrations, or other characteristics to appropriately define each batch

of the test or reference items should be known.

3. In cases where the test item is supplied by the sponsor, there should be a

mechanism, developed in cooperation between the sponsor and the test

facility, to verify the identity of the test item subject to the study.

4. The stability of test and reference items under storage and test conditions

should be known for all studies.

5. If the test item is administered or applied in a vehicle, the homogeneity,

concentration and stability of the test item in that vehicle should be

determined. For test items used in field studies (e.g. tank mixes), these

may be determined through separate laboratory experiments.

6. A sample for analytical purposes from each batch of test item should be

retained for all studies except short-term studies.

7. Standard operating procedures

1. A test facility should have written standard operating procedures approved by

test facility management that are intended to ensure the quality and integrity of

the data generated by that test facility. Revisions to standard operating procedures

should be approved by test facility management.

2. Each separate test facility unit or area should have immediately available current

standard operating procedures relevant to the activities being performed therein.

Published text books, analytical methods, articles and manuals may be used as

supplements to these standard operating procedures.

3. Deviations from standard operating procedures related to the study should be

documented and should be acknowledged by the study director and the principal

investigator(s), as applicable.

4. Standard operating procedures should be available for, but not be limited to, the

following categories of test facility activities. The details given under each

heading are to be considered as illustrative examples.

1. Test and reference items

Receipt, identification, labelling, handling, sampling and storage.

2. Apparatus, materials and reagents

(a)

Apparatus

use, maintenance, cleaning and calibration.

(b)

Computerised systems

validation, operation, maintenance, security, change control and

back-up.

(c)

Materials, reagents and solutions

preparation and labelling.

3. Record keeping, reporting, storage, and retrieval

Coding of studies, data collection, preparation of reports, indexing

systems, handling of data, including the use of computerised systems.

4. Test system (where appropriate)

(a)

Room preparation and environmental room conditions for the

test system.

(b)

Procedures for receipt, transfer, proper placement,

characterisation, identification and care of the test system.

(c)

Test system preparation, observations and examinations, before,

during and at the conclusion of the study.

(d)

Handling of test system individuals found moribund or dead

during the study.

(e)

Collection, identification and handling of specimens including

necropsy and histopathology.

(f)

Siting and placement of test systems in test plots.

5. Quality assurance procedures

Operation of Quality Assurance personnel in planning, scheduling,

performing, documenting and reporting inspections.

8. Performance of the study

8.1. Study plan

1. For each study, a written plan should exist prior to the initiation of the

study. The study plan should be approved by dated signature of the

study director and verified for GLP compliance by quality assurance

personnel as specified in 2.2(b) of Section II. The study plan should

also be appproved by the test facility management and the sponsor, if

required by national regulation or legislation in the country where the

study is being performed.

2. (a)

Amendments to the study plan should be justified and approved by

dated signature of the study director and maintained with the study plan.

(b) Deviations from the study plan should be described, explained,

acknowledged and dated in a timely fashion by the study director and/

or principal investigator(s) and maintained with the study raw data.

3. For short-term studies, a general study plan accompanied by a study specific

supplement may be used.

8.2. Content of the study plan

The study plan should contain, but not be limited to the following information

1. Identification of the study, the test item and reference item

(a)

a descriptive title;

(b)

a statement which reveals the nature and purpose of the study;

(c)

identification of the test item by code or name (IUPAC; CAS

number, biological parameters, etc.);

(d)

the reference item to be used.

2. Information concerning the sponsor and the test facility

(a)

name and address of the sponsor;

(b)

name and address of any test facilities and test sites involved;

(c)

name and address of the study director;

(d)

name and address of the principal investigator(s), and the

phase(s) of the study delegated by the study director and under

the responsibility of the principal investigator(s).

(a)

the date of approval of the study plan by signature of the study

director. The date of approval of the study plan by signature of

the test facility management and sponsor if required by national

regulation or legislation in the country where the study is being

performed;

(b)

the proposed experimental starting and completion dates.

4. Test methods

Reference to the OECD test guideline or other test guideline or method

to be used.

5. Issues (where applicable)

(a)

the justification for selection of the test system;

(b)

characterisation of the test system, such as the species, strain,

substrain, source of supply, number, body weight range, sex,

age and other pertinent information;

(c)

the method of administration and the reason for its choice;

(d)

the dose levels and/or concentration(s), frequency, and duration

of administration/application;

(e)

detailed information on the experimental design, including a

description of the chronological procedure of the study, all

methods, materials and conditions, type and frequency of

analysis, measurements, observations and examinations to be

performed, and statistical methods to be used (if any).

a list of records to be retained.

8.3. Conduct of the study

1. A unique identification should be given to each study. All items concerning

this study should carry this identification. Specimens from the study

should be identified to confirm their origin. Such identification should

enable traceability, as appropriate for the specimen and study.

2. The study should be conducted in accordance with the study plan.

3. All data generated during the conduct of the study should be recorded

directly, promptly, accurately, and legibly by the individual entering

the data. These entries should be signed or initialled and dated.

4. Any change in the raw data should be made so as not to obscure the previous

entry, should indicate the reason for change and should be dated and

signed or initialled by the individual making the change.

5. Data generated as a direct computer input should be identified at the time

of data input by the individual(s) responsible for direct data entries.

Computerised system design should always provide for the retention of

full audit trails to show all changes to the data without obscuring the

original data. It should be possible to associate all changes to data with

the persons having made those changes, for example, by use of timed

and dated (electronic) signatures. Reason for changes should be given.

9. Reporting of study results

9.1. General

1. A final report should be prepared for each study. In the case of short-term

studies, a standardized final report accompanied by a study specific

extension may be prepared.

2. Reports of principal investigators or scientists involved in the study should

be signed and dated by them.

3. The final report should be signed and dated by the study director to indicate

acceptance of responsibility for the validity of the data. The extent of

compliance with these principles of good laboratory practice should be

indicated.

4. Corrections and additions to a final report should be in the form of

amendments. Amendments should clearly specify the reason for the

corrections or additons and should be signed and dated by the study

director.

5. Reformatting of the final report to comply with the submission requirements

of a national registration or regulatory authority does not constitute a

correction, addition or amendment to the final report.

9.2. Content of the final report

The final report should include, but not be limited to, the following information

1. Identification of the study, the test item and reference item

(a)

a descriptive title;

(b)

identification of the test item by code or name (IUPAC, CAS

number, biological parameters, etc.);

(c)

identification of the reference item by name;

(d)

characterisation of the test item including purity, stability and

homogeneity.

2. Information concerning the sponsor and the test facility

(a)

name and address of the sponsor;

(b)

name and address of any test facilities and test sites involved;

(c)

name and address of the study director;

(d)

name and address of the principal investigator(s) and the

phase(s) of the study delegated, if applicable;

(e)

name and address of scientists having contributed reports to

the final report.

3. Dates

experimental starting and completion dates.

4. Statement

a quality assurance programme statement listing the types of inspections

made and their dates, including the phase(s) inspected, and the dates

any inspection results were reported to management and to the study

director and principal investigator(s), if applicable. This statement would

also serve to confirm that the final report reflects the raw data.

5. Description of materials and test methods

(a)

description of methods and materials used;

(b)

reference to OECD test guideline or other test guideline or

method.

6. Results

(a)

a summary of results;

(b)

all information and data required by the study plan;

(c)

a presentation of the results, including calculations and

determinations of statistical significance;

(d)

an evaluation and discussion of the results and, where

appropriate, conclusions.

7. Storage

the location(s) where the study plan, samples of test and reference items,

specimens, raw data and the final report are to be stored.

10. Storage and retention of records and materials

10.1. The following should be retained in the archives for the period specified by the

appropriate authorities

(a) the study plan, raw data, samples of test and reference items, specimens,

and the final report of each study;

(b) Records of all inspections performed by the quality assurance programme,

as well as master schedules;

(c) records of qualifications, training, experience and job descriptions of

personnel;

(d) records and reports of the maintenance and calibration of apparatus;

(e) validation documentation for computerised systems;

(f) the historical file of all standard operating procedures;

(g) environmental monitoring records.

In the absence of a required retention period, the final disposition of any study

materials should be documented. When samples of test and reference items

and specimens are disposed of before the expiry of the required retention period

for any reason, this should be justified and documented. Samples of test and

reference items and specimens should be retained only as long as the quality of

the preparation permits evaluation.

10.2. Material retained in the archives should be indexed so as to facilitate orderly

storage and retrieval.

10.3. Only personnel authorised by management should have access to the archives.

Movement of material in and out of the archives should be properly recorded.

10.4. If a test facility or an archive contracting facility goes out of business and has no

legal successor, the archive should be transferred to the archives of the sponsor(s)

of the study(s).

Mitbug[ fl-Istamperija tal-Gvern – Printed at the Government Printing Press